Increasing evidence has demonstrated that a local microenvironment, stem cell niche, is important in regulating their self-renewal and differentiation in tissue and organ development process. Stem cell niche provides a complex array of biochemical and physical cues in a spatiotemporally defined fashion, engaging and instructing stem cells to proliferate migrate and differentiate.
Such microenvironment consists of many factors including extracellular matrices (ECMs), growth factors, signaling molecules, etc. Although biochemical cues including soluble factors such as FGFs, BMPs and Wnts have been well studied for their role in regulating stem cell behavior, the effect of cell-matrix interaction in stem cell development is poorly understood.
Recapitulating the stem cell niche is a critical goal of regenerative medicine. Ideally, an engineered stem cell niche would include both spatial organization and dynamic modulation of cells, soluble factors, and matrix. While biomaterials technologies are being developed to address these needs, currently available matrices often lack this level of complexity. (See Kyle J. Lampe, et al., Building stem cell niches from the molecule up through engineered peptide materials, Neuroscience Letters (2012) 519:138-146; and M. P. Lutolf and J. A. Hubbell, Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering, Nature Biotechnology (2005) 23 (1):47-55.)
Many attempts have been made to create a synthetic stem cell niche by incorporating cell adhesion ligands into nanofiber or hydrogel-based scaffolds. For example, nanofiber-based scaffolds have been investigated for the regeneration of connective tissues, such as bone, meniscus, intervertebral disk, cartilage, tendons and ligaments. Nano-scale fibers have been shown to direct cell attachment and matrix deposition and represent an ideal system to model the collagenous matrices present within native tissue structures. These scaffolds exhibit high aspect ratio, surface area, permeability and porosity, and can be fabricated from a variety of polymers, both natural and synthetic, with tunable fiber diameter and matrix alignment.
A biochemically, mechanically and physically engineered nanofibrous microenvironment has been developed that mimics native extracellular microenvironments by presenting controlled fiber diameter, topography, pore size and elasticity of a matrix, as well as bioactive peptide motifs derived from extracellular matrix proteins on the nanofiber. Our engineered microenvironment can be used as an array of cell culture environments for screening of cell culture or tissue engineering environment by elucidating or regulating cellular behaviors such as cell adhesion, migration, growth, proliferation or morphogenesis as evidenced in stem cell assays.